Raman spectra are a unique fingerprint of chemical molecules that are produced by exciting the vibrational modes of the various atoms forming the molecule by using monochromatic light. The strength of the Raman scattered light relative to the incident light, is very small and usually requires a large amount of chemical molecules and high light powers for the spectra acquisition. Optical spectroscopy, such as Raman spectroscopy, is very important for the detection and recognition of biological molecules including, for example, cancer genes, important proteins and DNA nucleotides. Among these optical techniques, Surface-Enhanced Raman Scattering (“SERS” hereinafter) has attracted considerable attention since it may allow the investigation of exceedingly small sample volumes and even single molecules. However, practical application of this new tool turns out to be very difficult due to the complicated interpretation and low fidelity of the acquired spectra.
The reason for such difficulties lies in the mechanism of SERS: SERS is based on the huge amplification, by up to about 104, of the local optical fields at nanoscale roughness of metal substrates or metal nanoparticles (“hot spots”) that are induced by plasmon resonances. Molecules residing in these enhanced fields are so strongly excited that they can be detected in a Raman spectrum. Developing SERS based detectors and analyzers, however, faces a major challenge in the difficulty of finding SERS-active substrates that display these enhancements in both reliable and efficient ways. Currently there are several known commercial options available for unspecified and label-free SERS analysis. One option is from D3 Technologies (www.d3technologies.co.uk) and Mesophotonics (http://www.mesophotonics.com/sers_central/what_is_klarite.html), now part of Renishaw (http://www.renishawdiagnostics.com/en/klarite-sers-detection-substrates—12515). These technologies concern gold coated textured silicon based photonic crystal substrates that are fairly reliable but are not sensitive enough for single molecule detection. Another type of approach for SERS is from Real Time Analyzers Inc (www.rta.biz) offering vials of silver particles in a sol-gel solution. These latter “substrates” provide high sensitivity. However, there are only a few hot-spots randomly distributed in the vials and most of the solution is not SERS-active which yields spectra of low fidelity.